A small-molecule pan-HER inhibitor alone or in combination with cisplatin exerts efficacy against nasopharyngeal carcinoma

被引:1
作者
Yang, Jing [1 ,2 ,3 ,4 ]
Yang, Yanfei [1 ,2 ,5 ]
Wei, Yuquan [1 ,2 ]
Wei, Xiawei [1 ,2 ]
机构
[1] Sichuan Univ, Lab Aging Res & Canc Drug Target, State Key Lab Biotherapy, Natl Clin Res Ctr Geriatr,West China Hosp, Chengdu 610041, Peoples R China
[2] Sichuan Univ, West China Hosp, Canc Ctr, Natl Clin Res Ctr Geriatr, Chengdu 610041, Peoples R China
[3] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Melanoma & Sarcoma Med Oncol Unit, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Peoples R China
[4] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou 510060, Peoples R China
[5] Cent South Univ, Xiangya Hosp 3, Dept Gynecol & Obstet, Changsha 410008, Peoples R China
基金
美国国家科学基金会;
关键词
epidermal growth factor receptor; ErbB receptors; HM781-36B; nasopharyngeal carcinoma; molecular targeted therapy; cisplatin; GROWTH-FACTOR RECEPTOR; ANTITUMOR-ACTIVITY; TUMOR ANGIOGENESIS; DENDRITIC CELLS; ERBB RECEPTORS; CANCER; EXPRESSION; HM781-36B; DISCOVERY;
D O I
10.1007/s11684-022-0945-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The abnormal activation of HER family kinase activity is closely related to the development of human malignancies. In this study, we used HER kinases as targets for the treatment of nasopharyngeal carcinoma (NPC) and explored the anti-tumor effects of the novel pan-HER inhibitor HM781-36B, alone or in combination with cisplatin. We found that HER family proteins were positively expressed in tumor tissues of some NPC patients, and the high levels of those proteins were significantly related to poor prognosis. HM781-36B inhibited NPC in vitro and in vivo. HM781-36B exerted synergistic effects with cisplatin on inhibiting proliferation and promoting apoptosis of NPC cells. In NPC xenograft models in nude mice, HM781-36B and cisplatin synergistically inhibited tumor growth. Downregulating the activity of HER family proteins and their downstream signaling pathways and regulating tumor microenvironment may explain the synergistic anti-tumor effects of HM781-36B and cisplatin. In conclusion, our study provides evidence for HER family proteins as prognostic biomarkers and potential therapeutic targets for NPC. The pan-HER inhibitor HM781-36B alone or in combination with cisplatin represents promising therapeutic effects for the treatment of NPC patients, which provides a new idea for the comprehensive treatment of NPC.
引用
收藏
页码:275 / 289
页数:15
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